Evidence map›Paper›PMID 26428513›Full record

ReviewCancer treatment reviews2015

TAS-102, a novel antitumor agent: a review of the mechanism of action.

Heinz-Josef Lenz, Sebastian Stintzing, Fotios Loupakis

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Cancer treatment reviews, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 5 pooled it
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 5 syntheses or guidelines pooled it, 157 citations in OpenAlex.

  1. Pooled it
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  5. Oral versus intravenous fluoropyrimidines for colorectal cancer.The Cochrane database of systematic reviews · 2017
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  15. Analytical chemistry · 2026
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 3 institutions in 3 countries.

Heinz-Josef LenzUSC Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, NOR 3456, Los Angeles, CA 90089-9173, United States. Electronic address: lenz@usc.edu.
Sebastian StintzingDepartment of Hematology and Oncology, University Hospital Grosshadern, University of Munich (LMU), Marchioninistrasse 15, 81377 Munich, Germany. Electronic address: sebastian.stintzing@med.uni-muenchen.de.
Fotios LoupakisUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Via Taddeo Alderotti 26/N, 50139 Firenze, Italy. Electronic address: fotiosloupakis@gmail.com.
Azienda Ospedaliera Universitaria Pisana · ITLudwig-Maximilians-Universität München · DEUniversity of Southern California · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

Inhibition of nucleoside metabolism is an important principle in cancer therapy as evidenced by the role of fluoropyrimidines, such as 5-fluorouracil (5-FU), and antifolates in the treatment of many cancers. TAS-102 is an oral combination therapy consisting of trifluridine (FTD), a thymidine-based nucleoside analog, plus tipiracil hydrochloride (TPI), a novel thymidine phosphorylase inhibitor that improves the bioavailability of FTD. TAS-102 has demonstrated efficacy in 5-FU-refractory patients based on a different mechanism of action and has been approved for the treatment of metastatic colorectal cancer in Japan. This review describes the mechanism of action of TAS-102, highlighting key differences between TAS-102 and 5-FU-based therapies. While both FTD and 5-FU inhibit thymidylate synthase (TS), a central enzyme in DNA synthesis, sufficient TS inhibition by FTD requires continuous infusion; therefore, it is not considered a clinically relevant mechanism with oral dosing. Instead, the primary cytotoxic mechanism with twice-daily oral dosing, the schedule used in TAS-102 clinical development, is DNA incorporation. FTD incorporation into DNA induces DNA dysfunction, including DNA strand breaks. Uracil-based analogs such as 5-FU may also be incorporated into DNA; however, they are immediately cleaved off by uracil-DNA glycosylases, reducing their ability to damage DNA. Moreover, the TPI component may enhance the durability of response to FTD. With its distinct mechanism of action and metabolism, TAS-102 is a promising treatment option for patients resistant to or intolerant of 5-FU-based fluoropyrimidines.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsClinical Trials as TopicDrug CombinationsHumansNeoplasmsPyrrolidinesThymineTrifluridineUracilDrug CombinationsPyrrolidinesThymineTrifluridinetrifluridine tipiracil drug combinationUracil5-FluorouracilFluoropyrimidinesMechanism of actionMetastatic colorectal cancerTAS-102Thymidylate synthase

Identifiers

PMID26428513
PMCPMC4624296
OpenAlexW1889053010

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.